Approximately one out of five adults in the United States has some degree of hearing loss. The most common types of hearing loss is sensorineural (i.e., related to inner ear dysfunction). A prominent signature of the sensorineural hearing loss is damage of outer hair cells, which can result in 40-60 dB of hearing loss. Thus the outer hair cells are central to cochlear amplification. The cochlear amplification is a balancing act between the dissipation of energy during vibrations of cochlear epithelium and the compensation of energy by the outer hair cells. The force generation by the outer hair cells has been a hot topic in hearing research, and there has been great progress on that aspect of cochlear amplification. This project will expand the horizon of hearing research in two ways. First, it will focus on the interactions between the outer hair cells and their supporting cells an tissues. The organ of Corti is a cellular complex that mediates the interaction between outer hair cells and their extra-cellular structures that are responsible for cochlear frequency tuning. Secondly, this project will clarify the balancing act in the cochlea by investigating an underappreciated-but-crucial aspect - the energy dissipation. We have a long-term ambition to explain some hearing abnormalities with the view of an imbalance between dissipation and compensation mechanisms in the organ of Corti. This project will be an essential step toward the goal. The primary hypothesis of the project is that the organ of Corti is a micro-machine that optimizes power transmission from the outer hair cell to the stereociliary bundle of the inner hair cell for sound amplification and frequency selectivity. To test this hypothesis, three specific aim were established: 1) to identify the mechanical contribution of the tectorial membrane - an extra-cellular structure overlying the outer hair cells, 2) to examine the source and role of resistive damping in the organ of Corti, and 3) to examine the power flux due to outer hair cell motility. This project uses a detailed computational model of the organ of Corti and a novel experimental approach to observe the multi-cellular physics of the organ of Corti complex. The computational model is focused on the interactions between active outer hair cells and their surrounding micro-structures. This project will take full advantage of existing achievements of macro cochlear biophysics by coupling cochlear fluid dynamics with multi-cellular biophysics of the organ of Corti. The experimental approach will facilitate the computational model to draw more concrete conclusions about cochlear power transmission. A novel micro-fluidic chamber system will allow us to control the mechanical, chemical and electrical conditions of the organ of Corti. The results of this project will explain how acoustic energy dissipates in the organ of Corti. A clinically relevant example of the imbalance between dissipation and compensation will be investigated - the spontaneous otoacoustic emission.